A functional role for the B56 alpha-subunit of protein phosphatase 2A in ceramide-mediated regulation of Bcl2 phosphorylation status and function.
Authors Ruvolo Peter P; Clark Warren; Mumby Marc; Gao Fengqin; May W Stratford;
JournalJ Biol Chem
PubMed ID11929874
'Recently it has been shown that the potent apoptotic agent ceramide activates a mitochondrial protein phosphatase 2A (PP2A) and promotes dephosphorylation of the anti-apoptotic molecule Bcl2 (Ruvolo, P. P., Deng, X., Ito, T., Carr, B. K., and May, W. S. (1999) J. Biol. Chem. 274, 20296-20300). In cells expressing Bcl2, ... More
Metabolism of 4 beta -hydroxycholesterol in humans.
'One of the major oxysterols in the human circulation is 4 beta-hydroxycholesterol formed from cholesterol by the drug-metabolizing enzyme cytochrome P450 3A4. Deuterium-labeled 4 beta-hydroxycholesterol was injected into two healthy volunteers, and the apparent half-life was found to be 64 and 60 h, respectively. We have determined earlier the half-lives ... More
Activation of retinoic acid receptor-dependent transcription by all-trans-retinoic acid metabolites and isomers.
Authors Idres Nadia; Marill Julie; Flexor Maria A; Chabot Guy G;
JournalJ Biol Chem
PubMed ID12070176
'We have shown that four metabolites of all-trans-retinoic acid (ATRA) (4-oxo-, 4-OH-, 18-OH-, and 5,6-epoxy-RA) can induce maturation of NB4 promyelocytic leukemia cells (Idres, N., Benoit, G., Flexor, M. A., Lanotte, M., and Chabot, G. G. (2001) Cancer Res. 61, 700-705). To better understand the mechanism of action of ATRA ... More
Interaction of human breast fibroblasts with collagen I increases secretion of procathepsin B.
Authors Koblinski Jennifer E; Dosescu Julie; Sameni Mansoureh; Moin Kamiar; Clark Katherine; Sloane Bonnie F;
JournalJ Biol Chem
PubMed ID12072442
'Interactions of stromal and tumor cells with the extracellular matrix may regulate expression of proteases including the lysosomal proteases cathepsins B and D. In the present study, we determined whether the expression of these two proteases in human breast fibroblasts was modulated by interactions with the extracellular matrix component, collagen ... More
A ligand-inducible epidermal growth factor receptor/anaplastic lymphoma kinase chimera promotes mitogenesis and transforming properties in 3T3 cells.
'Oncogenic rearrangements of the anaplastic lymphoma kinase (ALK) gene, encoding a receptor type tyrosine kinase, are frequently associated with anaplastic large cell lymphomas. Such rearrangements juxtapose the intracellular domain of ALK to 5''-end sequences belonging to different genes and create transforming fusion proteins. To understand how the oncogenic versions of ... More
Simulated microgravity culture system for a 3-D carcinoma tissue model.
AuthorsNakamura K, Kuga H, Morisaki T, Baba E, Sato N, Mizumoto K, Sueishi K, Tanaka M, Katano M,
JournalBiotechniques
PubMed ID12449385
'An in vitro organotypic culture model is needed to understand the complexities of carcinoma tissue consisting of carcinoma cells, stromal cells, and extracellular matrices. We developed a new in vitro model of carcinoma tissue using a rotary cell culture system with four disposable vessels (RCCS-4D) that provides a simulated microgravity ... More
Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells: protective role in apoptosis.
'Hypoxia is a common environmental stress that influences signaling pathways and cell function. Several cell types, including neuroendocrine chromaffin cells, have evolved to sense oxygen levels and initiate specific adaptive responses to hypoxia. Here we report that under hypoxic conditions, rat pheochromocytoma PC12 cells are resistant to apoptosis induced by ... More
Antagonism between Ena/VASP Proteins and Actin Filament Capping Regulates Fibroblast Motility.
Authors Bear James E; Svitkina Tatyana M; Krause Matthias; Schafer Dorothy A; Loureiro Joseph J; Strasser Geraldine A; Maly Ivan V; Chaga Oleg Y; Cooper John A; Borisy Gary G; Gertler Frank B;
JournalCell
PubMed ID12086607
'Cell motility requires lamellipodial protrusion, a process driven by actin polymerization. Ena/VASP proteins accumulate in protruding lamellipodia and promote the rapid actin-driven motility of the pathogen Listeria. In contrast, Ena/VASP negatively regulate cell translocation. To resolve this paradox, we analyzed the function of Ena/VASP during lamellipodial protrusion. Ena/VASP-deficient lamellipodia protruded ... More
Interactions between protein kinase CK2 and Pin1. Evidence for phosphorylation-dependent interactions.
Authors Messenger Moira M; Saulnier Ronald B; Gilchrist Andrew D; Diamond Phaedra; Gorbsky Gary J; Litchfield David W;
JournalJ Biol Chem
PubMed ID11940573
'The peptidyl-prolyl isomerase Pin1 interacts in a phosphorylation-dependent manner with several proteins involved in cell cycle events. In this study, we demonstrate that Pin1 interacts with protein kinase CK2, an enzyme that generally exists in tetrameric complexes composed of two catalytic CK2 alpha and/or CK2 alpha'' subunits together with two ... More
Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein.
AuthorsElomaa O, Pulkkinen K, Hannelius U, Mikkola M, Saarialho-Kere U, Kere J,
JournalHum Mol Genet
PubMed ID11309369
'Anhidrotic ectodermal dysplasia (EDA) is an X-linked disorder characterized by abnormal development of ectoderm and its appendices. The EDA gene encodes different isoforms of ectodysplasin, a transmembrane protein. The two longest isoforms, ectodysplasin-A1 and -A2, which differ by an insertion of two amino acids, are trimeric type II membrane proteins ... More
Aldose reductase mediates mitogenic signaling in vascular smooth muscle cells.
'Abnormal vascular smooth muscle cell (VSMC) proliferation is a key feature of atherosclerosis and restenosis; however, the mechanisms regulating growth remain unclear. Herein we show that inhibition of the aldehyde-metabolizing enzyme aldose reductase (AR) inhibits NF-kappa B activation during restenosis of balloon-injured rat carotid arteries as well as VSMC proliferation ... More
Membrane topology influences N-glycosylation of the prion protein.
AuthorsWalmsley AR, Zeng F, Hooper NM,
JournalEMBO J
PubMed ID11179215
'The glycosylation state of the glycosyl-phosphatidylinositol (GPI) anchored cellular prion protein (PrPC) can influence the formation of the disease form of the protein responsible for the neurodegenerative spongiform encephalopathies. We have investigated the role of membrane topology in the N-glycosylation of PrP by expressing a C-terminal transmembrane anchored form, PrP-CTM, ... More
Cell adhesion and migration properties of beta 2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation.
AuthorsSixt M, Hallmann R, Wendler O, Scharffetter-Kochanek K, Sorokin LM,
JournalJ Biol Chem
PubMed ID11278780
'Regulated adhesion of leukocytes to the extracellular matrix is essential for transmigration of blood vessels and subsequent migration into the stroma of inflamed tissues. Although beta(2)-integrins play an indisputable role in adhesion of polymorphonuclear granulocytes (PMN) to endothelium, we show here that beta(1)- and beta(3)-integrins but not beta(2)-integrin are essential ... More
Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex.
'The survival of motor neurons (SMN) protein is the product of the gene mutated or deleted in the neurodegenerative disease, spinal muscular atrophy. SMN is part of a large macromolecular complex that also contains Gemin2, Gemin3, Gemin4, Gemin5, and Gemin6. The SMN complex functions in the assembly of spliceosomal small ... More
Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O.
AuthorsWalev I, Bhakdi SC, Hofmann F, Djonder N, Valeva A, Aktories K, Bhakdi S,
JournalProc Natl Acad Sci U S A
PubMed ID11248053
'The pore-forming toxin streptolysin O (SLO) can be used to reversibly permeabilize adherent and nonadherent cells, allowing delivery of molecules with up to 100 kDa mass to the cytosol. Using FITC-labeled albumin, 10(5)-10(6) molecules were estimated to be entrapped per cell. Repair of toxin lesions depended on Ca(2+)-calmodulin and on ... More
Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores.
AuthorsSharma G, Vijayaraghavan S,
JournalProc Natl Acad Sci U S A
PubMed ID11259680
In this report we provide evidence that neuronal nicotinic acetylcholine receptors (nAChRs) are present on hippocampal astrocytes and their activation produces rapid currents and calcium transients. Our data indicate that these responses obtained from astrocytes are primarily mediated by an AChR subtype that is functionally blocked by alpha-bungarotoxin (alpha Bgt) ... More
Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7.
AuthorsArdley HC, Tan NG, Rose SA, Markham AF, Robinson PA,
JournalJ Biol Chem
PubMed ID11278816
We recently reported the identification of a RING finger-containing protein, HHARI (human homologue of Drosophila ariadne), which binds to the human ubiquitin-conjugating enzyme UbcH7 in vitro. We now demonstrate that HHARI interacts and co-localizes with UbcH7 in mammalian cells, particularly in the perinuclear region. We have further defined a minimal ... More
The giant protein AHNAK is a specific target for the calcium- and zinc-binding S100B protein: potential implications for Ca2+ homeostasis regulation by S100B.
Transformation of rat embryo fibroblast clone 6 cells by ras and temperature-sensitive p53val(135) is reverted by ectopic expression of the calcium- and zinc-binding protein S100B. In an attempt to define the molecular basis of the S100B action, we have identified the giant phosphoprotein AHNAK as the major and most specific ... More
Apoptosis induces efflux of the mitochondrial matrix enzyme deoxyguanosine kinase.
AuthorsJüllig M, Eriksson S,
JournalJ Biol Chem
PubMed ID11294860
Deoxyguanosine kinase (dGK) initiates the salvage of purine deoxynucleosides in mitochondria and is a key enzyme in mitochondrial DNA precursor synthesis. The active form of the enzyme is a 60-kDa protein normally located in the mitochondrial matrix. Here we describe the subcellular distribution of dGK during apoptosis in human epithelial ... More
A novel specific role for I kappa B kinase complex-associated protein in cytosolic stress signaling.
We demonstrate here a novel role for the I kappa B kinase complex-associated protein (IKAP) in the regulation of activation of the mammalian stress response via the c-Jun N-terminal kinase (JNK)-signaling pathway. We cloned IKAP as a JNK-associating protein using the Ras recruitment yeast two-hybrid system. IKAP efficiently and specifically ... More
Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1.
Authors Wong Wai K; Ou Xiao-Ming; Chen Kevin; Shih Jean C;
JournalJ Biol Chem
PubMed ID11956220
Monoamine oxidases (MAO) A and B deaminate a number of biogenic amines. Aberrant expression of MAO is implicated in several psychiatric and neurogenerative disorders. In this study, we have shown that phorbol 12-myristate 13-acetate (PMA) increases human MAO B, but not MAO A, gene expression. The sequence between -246 and ... More
Krüppel-like zinc fingers bind to nuclear import proteins and are required for efficient nuclear localization of erythroid Krüppel-like factor.
Authors Quadrini Karen J; Bieker James J;
JournalJ Biol Chem
PubMed ID12072445
Erythroid Krüppel-like Factor (EKLF/KLF-1) is an erythroid-specific transcription factor that contains three C(2)H(2) zinc fingers and is required for correct chromatin structure and expression of the beta-globin locus. However, regions within the EKLF protein that serve as signals for its nuclear localization and the proteins that may enable it to ... More
Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival.
Authors Sotiriou Sotiria; Gispert Suzana; Cheng Jun; Wang Yaohui; Chen Amy; Hoogstraten-Miller Shelley; Miller Georgina F; Kwon Oran; Levine Mark; Guttentag Susan H; Nussbaum Robert L;
JournalNat Med
PubMed ID11984580
The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen. We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, ... More
A novel lipoarabinomannan from the equine pathogen Rhodococcus equi. Structure and effect on macrophage cytokine production.
Rhodococcus equi is a major cause of foal morbidity and mortality. We have investigated the presence of lipoglycan in this organism as closely related bacteria, notably Mycobacterium tuberculosis, produce lipoarabinomannans (LAM) that may play multiple roles as virulence determinants. The lipoglycan was structurally characterized by gas chromatography-mass spectrometry following permethylation, ... More
Cholesterol modulates the membrane binding and intracellular distribution of annexin 6.
Authors de Diego Iñaki; Schwartz Felix; Siegfried Heide; Dauterstedt Paul; Heeren Joerg; Beisiegel Ulrike; Enrich Carlos; Grewal Thomas;
JournalJ Biol Chem
PubMed ID12070178
Annexins are Ca(2+)- and phospholipid-binding proteins that are widely expressed in mammalian tissues and that bind to different cellular membranes. In recent years its role in membrane traffic has emerged as one of its predominant functions, but the regulation of its intracellular distribution still remains unclear. We demonstrated that annexin ... More
Regulation of calreticulin expression during induction of differentiation in human myeloid cells. Evidence for remodeling of the endoplasmic reticulum.
Authors Clark Robert A; Li Sen-Lin; Pearson Doran W; Leidal Kevin G; Clark Joshua R; Denning Gerene M; Reddick Robert; Krause Karl-Heinz; Valente Anthony J;
JournalJ Biol Chem
PubMed ID12065601
Induction of differentiation of HL-60 human myeloid cells profoundly affected expression of calreticulin, a Ca(2+)-binding endoplasmic reticulum chaperone. Induction with Me(2)SO or retinoic acid reduced levels of calreticulin protein by approximately 60% within 4 days. Pulse-chase studies indicated that labeled calreticulin decayed at similar rates in differentiated and undifferentiated cells ... More
Elucidation of structure and biological properties of the prion protein scrapie (PrP(Sc)) is fundamental to an understanding of the mechanism of conformational transition of cellular (PrP(C)) into disease-specific isoforms and the pathogenesis of prion diseases. Unfortunately, the insolubility and heterogeneity of PrP(Sc) have limited these studies. The observation that a ... More
Glycogen synthase kinase 3beta is activated by cAMP and plays an active role in the regulation of melanogenesis.
In human and mouse, cAMP plays a key role in the control of pigmentation. cAMP, through the activation of protein kinase A, increases the expression of microphthalmia-associated transcription factor (MITF), which in turn stimulates tyrosinase gene expression, to allow melanin synthesis. Beyond this simplified scheme, cAMP inhibits phosphatidylinositol 3-kinase (PI3K), ... More
Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta.
Authors Keshamouni Venkateshwar G; Mattingly Raymond R; Reddy Kaladhar B;
JournalJ Biol Chem
PubMed ID11960991
Activation of mitogen-activated protein kinase (Erk/MAPK) is a critical signal transduction event for estrogen (E(2))-mediated cell proliferation. Recent studies from our group and others have shown that persistent activation of Erk plays a major role in cell migration and tumor progression. The signaling mechanism(s) responsible for persistent Erk activation are ... More
A 2-D liquid separations/mass mapping method for interlysate comparison of ovarian cancers.
Authors Kachman Maureen T; Wang Haixing; Schwartz Donald R; Cho Kathleen R; Lubman David M;
JournalAnal Chem
PubMed ID11985308
A two-dimensional liquid phase separation of proteins from whole cell lysates coupled on-line to an electrospray-ionization time-of-flight (ESI-TOF) mass spectrometer (MS) is used to map the protein content of ovarian surface epithelial cells (OSE) and an ovarian carcinoma-derived cell line (ES2). The two dimensions involve the use of liquid isoelectric ... More
Raloxifene improves endothelial dysfunction in hypertension by reduced oxidative stress and enhanced nitric oxide production.
BACKGROUND: It has not been completely clarified whether selective estrogen receptor modulators (SERMs) such as raloxifene exert vasoprotective effects similar to those of estrogens. METHODS AND RESULTS: To investigate vascular effects of raloxifene, male spontaneously hypertensive rats were treated for 10 weeks with either raloxifene (10 mg x kg(-1) x ... More
Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity.
Authors Yu Jinghua; Lo Jane-L; Huang Li; Zhao Annie; Metzger Edward; Adams Alan; Meinke Peter T; Wright Samuel D; Cui Jisong;
JournalJ Biol Chem
PubMed ID12052824
Bile salt export pump (BSEP) is a major bile acid transporter in the liver. Mutations in BSEP result in progressive intrahepatic cholestasis, a severe liver disease that impairs bile flow and causes irreversible liver damage. BSEP is a target for inhibition and down-regulation by drugs and abnormal bile salt metabolites, ... More
Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo.
Authors Kim Eun-Joo; Park Jong-Sup; Um Soo-Jong;
JournalJ Biol Chem
PubMed ID11925430
To study the biological role of p73 alpha, a member of the p53 tumor suppressor family, we performed a yeast two-hybrid screen of a human cDNA library. Using a p73 alpha fragment consisting of amino acids 49-636 as bait, we found that p73 alpha is functionally associated with the human ... More